Development of novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists.
Novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives were identified as potent human H(3) receptor inverse agonists. After systematic modification of lead 5a, the potent and selective analog 5r was identified. Elimination of hERG K(+) channel and human alpha(1A)-adrenoceptor activities is the main focus of the present study.
Mizutani
Takashi
T
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan.
Nagase
Tsuyoshi
T
Ito
Sayaka
S
Miyamoto
Yasuhisa
Y
Tanaka
Takeshi
T
Takenaga
Norihiro
N
Tokita
Shigeru
S
Sato
Nagaaki
N
D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists; D001921:Brain / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D017442:Histamine Agonists / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D052999:Quinazolinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D058668:Adrenergic alpha-1 Receptor Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D017442:Histamine Agonists; C000606913:KCNH2 protein, human; D052999:Quinazolinones